Author

Date of Award

Degree Name

Department

First Advisor

Dr. John Spitsbergen

Second Advisor

Dr. Cindy Linn

Third Advisor

Dr. Christine Byrd-Jacobs

Access Setting

Masters Thesis-Campus Only

Restricted to Campus until

2-15-2018

Abstract

Glial cell line-derived neurotrophic factor (GDNF) is an important signaling molecule for the somatic motor nervous system. GDNF protein is produced and secreted by skeletal muscle cells and helps maintain motor neuron innervation at the neuromuscular junction. Treatment with exogenous GDNF prevents denervation which is characteristic of aging and neurodegenerative disease. The therapeutic potential of GDNF cannot be fully explored without understanding the mechanisms by which GDNF protein production is regulated. The primary objective of this study was to determine the role of calcium in regulating GDNF protein expression by skeletal muscle cells. Skeletal muscle cells (C2C12) were grown in culture and allowed to differentiate into myotubes. The following treatments were given: Bay K8644 (100μM), an agonist for L-type calcium channels, nifedipine (100μM), a known antagonist for voltage-gated L-type calcium channels, and dantolene (100μM), an antagonist for ryanodine channels. Results suggest that expression of GDNF in skeletal muscle is regulated in a calcium-dependent manner. Acquiring a greater understanding of the role that calcium plays in regulating GDNF production may help to identify potential sites for therapeutic intervention to increase or decrease GDNF production. NSF Grant DBI-1062883 and NIH Grant 1R15AG022908-01A2